Compositions of flavones and long chain fatty acid derivatives isolated from plants and methods related thereto for the control of prostate disorders

Abstract

Disclosed herein is the extraction, separation, and preparation of plant medicinal extracts to provide compositions containing enriched and isolated flavone derivatives of formula I and long chain fatty acid derivatives of formula II from natural plants, wherein R 1 , R 2 , R 3 , R 4 , R 5 , X, A, B and n 1 are as defined in the specification. These extracts are used to control, i.e., prevent and treat, prostate diseases.

1 . A medicinal composition comprising a therapeutically effective amount of at least one isolated flavone derivative of formula I and/or a therapeutically effective amount of at least one isolated long chain fatty acid derivative of formula II  
     
       
         
         
             
             
         
       
     
     wherein 
 R 1  is OH, alkoxy, glucosyloxy or rhamnosyloxy;  
 R 2  is H, OH or alkoxy;  
 R 3  is H, OH, alkoxy or -Q 1 -Q 2 -(Q 3 ) n , wherein Q 1  is 0, S, or N; Q 2  is rhamnosyl or glucosyl; Q 3  is cinnamyl, cinnamoyloxy containing hydroxyl or benzoyloxy containing hydroxyl, n is an integer from 0 to 5;  
 R 4  is OH or alkoxyl;  
 R 5  is OH, alkoxyl, glucosyloxy or rhamnosyloxy;  
 X is a single bond or double bond; and  
                     
 wherein  
 A is (CH 2 ) n2  or (CH 2 —CH═CH) n3 , wherein n 2 , n 3  are integer from 0 to 20 independently;  
 B is N-ethoxyl, 1-O-fructoside, glyceryl or OH;  
 n 1  is an integer from 0 to 20.  
 
   
   
       2 . A medicinal composition according to  claim 1  wherein the flavone derivative of formula I: 
 R 1  is OH;    R 2  is H;    R 3  is H;    R 4  is OH;    R 5  is OH;    X is a single bond (naringenin).    
   
   
       3 . A medicinal composition according to  claim 1  wherein the flavone derivative of formula I: 
 R 1  is OH;    R 2  is H;    R 3  is OH;    R 4  is OH;    R 5  is OH;    X is a single bond (kaempferol).    
   
   
       4 . A medicinal composition according to  claim 1  wherein the flavone derivative of formula I: 
 R 1  is OH;    R 2  is OH;    R 3  is H;    R 4  is OH;    R 5  is OH;    X is a single bond (luteolin).    
   
   
       5 . A medicinal composition according to  claim 1  wherein the flavone derivative of formula I: 
 R 2  is H;    R 3  is -Q 1 -Q 2 -(Q 3 ) n , wherein Q 1  is O; Q 2  is rhamnosyl; Q 3  is cinnamyl, n is 1;    R 4  is OH;    R 5  is OH;    X is a double bond (kaemferol 3-O-(3″-O-cinnamoyl)-α-L-rhamnopyranoside).    
   
   
       6 . A medicinal composition according to  claim 1  wherein the flavone derivative of formula I: 
 R 1  is OH;    R 2  is H;    R 3  is -Q 1 -Q 2 -(Q 1 ) n , wherein Q 1  is O; Q 2  is rhamnosyl; Q 3  is cinnamyl, n is 2;    R 4  is OH;    R 5  is OH;    X is a double bond (kaemferol 3-O-(2″,3″-O-dicirmamoyl)-α-L-rhamnopyranoside).    
   
   
       7 . A medicinal composition according to  claim 1  wherein the long chain fatty acid derivative of formula II: 
 A is (CH 2 —CH═CH) n3 , wherein n 3  is 3;    B is glyceryl;    n 1  is 7 (linolenic acid glycerin ester).    
   
   
       8 . A medicinal composition according to  claim 1  wherein the long chain fatty acid derivative of formula II: 
 A is (CH 2 —CH═CH) n3 , wherein n 3  is 3;    B is N-ethoxyl;    n 1  is 7 (N-(2-ethoxyl)-9,12,15-linolenamide).    
   
   
       9 . A medicinal composition according to  claim 1  wherein the long chain fatty acid derivative of formula II: 
 A is (CH 2 —CH═CH) n3 , wherein n 3  is 3;    B is 1-O-fructoside;    n 1  is 7 (9,12,15-octadecatrienoic acid 1-O-β-D-fructoside).    
   
   
       10 . A medicinal composition according to  claim 1  wherein the long chain fatty acid derivative of formula II: 
 A is (CH 2 ) n2 , wherein n 2  is 13;    B is 1-O-fructoside;    n 1  is 1 (hexadecanoic 1-O-β-D-fructoside).    
   
   
       11 . A medicinal composition according to  claim 1  which comprises at least one pharmaceutically acceptable excipient, carrier, or diluent.  
   
   
       12 . A medicinal composition according to  claim 11  in a dosage form selected from the group consisting of tablet, powder, capsule, solution for oral administration, granule, decoctum, pill, pulvi, suspension, dispersant, syrup, suppository, and solution for parenteral administration.  
   
   
       13 . A composition according to  claim 11  indicated for the treatment of a prostate pathological disorder or an abnormal prostate condition.  
   
   
       14 . The composition of  claim 11  in unit dosage form, comprising from 0.01 to 1000 mg of at least one isolated flavone derivative of formula I and/or at least one isolated long chain fatty acid derivative of formula II.  
   
   
       15 . The composition of  claim 14  in unit dosage form, comprising 0.5 to 500 mg of at least one isolated flavone derivative of formula I and/or at least one isolated long chain fatty acid derivative of formula II.  
   
   
       16 . A process for the preparation of a medicinal composition comprising a therapeutically effective amount of at least one isolated flavone derivative of formula I and/or a therapeutically effective amount of at least one isolated long chain fatty acid derivative of formula II  
     
       
         
         
             
             
         
       
     
     wherein 
 R 1  is OH, alkoxy, glucosyloxy or rhamnosyloxy;  
 R 2  is H, OH or alkoxy;  
 R 3  is H, OH, alkoxy or -Q 1 -Q 2 -(Q 3 ) n , wherein Q 1  is 0, S, or N; Q 2  is rhamnosyl or glucosyl; Q 3  is cinnamyl, cinnamoyloxy containing hydroxyl or benzoyloxy containing hydroxyl, n is an integer from 0 to 5;  
 R 4  is OH or alkoxyl;  
 R 5  is OH, alkoxyl, glucosyloxy or rhamnosyloxy;  
 X is a single bond or double bond; and  
                     
 wherein  
 A is (CH 2 ) n  or (CH 2 —CH═CH) n3 , wherein n 2 , n 3  are integer from 0 to 20 independently;  
 B is N-ethoxyl, 1-O-fructoside, glyceryl or OH;  
 n 1  is an integer from 0 to 20; and  
 wherein the process comprises the steps of:  
 smashing plant material,  
 extracting resulting smashed plant material with at least one solvent, and  
 purifying the flavone derivatives and/or long chain fatty acid derivatives by column chromatography.  
 
   
   
       17 . The preparation process according to  claim 16  wherein an extraction solvent is selected from the group consisting essentially of water, methanol, ethanol, acetone, methanol-water, ethanol-water, acetone-water or ethyl acetate; and, 
 a method of extracting is reflux extraction or ultrasound extraction.    
   
   
       18 . The preparation process according to  claim 16 , further comprising a degreasing extraction step after the first extracting step wherein a degreasing solvent is selected from the group consisting essentially of hexane, cyclohexane, chloroform, petroleum ether and ether.  
   
   
       19 . The preparation process according to  claim 16 , wherein the chromatography is silica gel column chromatography, polyamine column chromatography, or sephadex LH20 column chromatography.  
   
   
       20 . The preparation process according to  claim 19 , wherein solvents used in gradient elution of silica gel column chromatography comprise two solvents selected from the group consisting essentially of petroleum ether, ethyl acetate, cyclohexane, acetone and hexane.